Cyclic hexapeptides

Abstract

Synthetic novel cyclic hexapeptides having the structure: Cyclo[(N-alkylamino acid)-X-(N-alkylamino acid)'-X-(N-alkylamino acid)"-X] wherein (N-alkylamino acid), (N-alkylamino acid)' and (N-alkylamino acid)" have the structure: ##STR1## wherein R 1 is a lower alkyl group having 1 to 3 carbon atoms and R 2 is hydrogen and methyl or R 1 and R 2 are --CH 2 --N, n being an integer 2 or 3, and form a 4- or 5- membered ring; and X is D- or L-Ala, D- or L-Phe, D- or L-Leu, D- or L-p-halophenylalanyl or D- or L-p-nitrophenylalanyl, with the proviso that when R 1 is methyl and R 2 is hydrogen, X is not D-Ala are prepared. Oral administration of these cyclic peptides improves the digestive efficiency of certain herbivorous animals.

What is claimed is: 
     
       1. The peptides having the structure: cyclo[(N-alkylamino acid)-X-(N-alkylamino acid)'-X-(N-alkylamino acid)"-X] wherein (N-alkylamino acid), (N-alkylamino acid)' and (N-alkylamino acid)" have the structure: ##STR6## wherein R 1  is a lower alkyl group having 1 to 3 carbon atoms and R 2  is hydrogen and methyl or R 1  and R 2  are --CH 2  -- n , n being an integer 2 or 3, and form a 4- or 5-membered ring; and X is D- or L-Ala, D- or L-Phe, D- or L-Leu, D- or L-p-halophenylalanyl or D- or L-p-nitrophenylalanyl, with the proviso that when R 1  is methyl and R 2  is hydrogen, X is not D-Ala.     
     
     
       2. The peptides according to claim 1 wherein (N-alkylamino acid), (N-alkylamino acid)' and (N-alkylamino acid)" are selected from the group consisting of Sar, D- or L-Pro and X is D- or L-Ala or D- or L-Phe and wherein when Pro is D, X is L-Ala or L-Phe or L-p-chlorophenylalanyl or L-p-nitrophenylalanyl; and when Pro is L, X is D-Ala or D-Phe or D-p-chlorophenylalanyl or D-p-nitrophenylalanyl; and wherein when N-alkylamino acid is Sar, X is not D-Ala or D- or L-Phe. 
     
     
       3. The peptides according to claim 2 having the structure: cyclo(D-Pro-Ala) 3 , cyclo(D-Pro-Phe) 3 , cyclo(Pro-D-Phe) 3 , cyclo(Sar-Ala) 3 , cyclo(Pro-D-Ala) 3 , cyclo(Sar-D-Phe) (Pro-D-Phe) 2 , and cyclo(p-chlorophenylalanyl-D-Pro) 3 .   
     
     
       4. The peptide according to claim 3 having the structure: ##STR7## 
     
     
       5. The peptide according to claim 3 having the structure: ##STR8## 
     
     
       6. The peptide according to claim 3 having the structure: ##STR9## 
     
     
       7. A composition useful for increasing the efficiency of feed utilization by ruminant animals having a developed rumen function comprising an inert carrier and a VFA-increasing amount of the peptide having the structure: cyclo[(N-alkylamino acid)-X-(N-alkylamino acid)'-X-(N-alkylamino acid)"-X] wherein (N-alkylamino acid), (N-alkylamino acid)' and (N-alkylamino acid)" have the structure: ##STR10## wherein R 1  is a lower alkyl group having 1 to 3 carbon atoms and R 2  is hydrogen and methyl or R 1  and R 2  are --CH 2  -- n , n being an integer 2 or 3, and form a 4- or 5-membered ring; and X is D- or L-Ala, D- or L-Phe, D- or L-Leu, D- or L-p-halophenylalanyl or D- or L-p-nitrophenylalanyl, with the proviso that when R 1  is methyl and R 2  is hydrogen, X is not D-Ala.     
     
     
       8. A composition according to claim 7 wherein said compound comprises from about 0.00005 to about 0.5% by weight of said composition. 
     
     
       9. A composition according to claim 7 wherein said compound comprises from about 0.00025 to about 0.1% by weight of said composition. 
     
     
       10. A concentrated premix composition for addition to the feed of a ruminant, useful for the increased utilization of feed, which comprises from about 0.1 to about 50% by weight of the peptide having the structure: cyclo[(N-alkylamino acid)-X-(N-alkylamino acid)'-X-(N-alkylamino acid)"-X] wherein (N-alkylamino acid), (N-alkylamino acid)' and (N-alkylamino acid)" have the structure: ##STR11## wherein R 1  is a lower alkyl group having 1 to 3 carbon atoms and R 2  is hydrogen and methyl or R 1  and R 2  are --CH 2  -- n , n being an integer 2 or 3, and form a 4- or 5-membered ring; and X is D- or L-Ala, D- or L-Phe, D- or L-Leu, D- or L-p-halophenylalanyl or D- or L-p-nitrophenylalanyl, with the proviso that when R 1  is methyl and R 2  is hydrogen, X is not D-Ala and an inert carrier.     
     
     
       11. The concentrated premix composition of claim 10 which comprises from about 2 to about 25% by weight of said peptide.